Evaluation of the safety, recovery, half-life, and clinical efficacy of antithrombin III (human) in patients with hereditary antithrombin III deficiency. Cooperative Study Group [see comments]

Ménaché, D; O'Malley, J; Jb, Schorr; Wagner, Bianca; Williams, Craigenne; Bm, Alving; Ballard, JO; Sh, Goodnight; Hathaway, W. E.; Hultin, Mae B.

doi:10.1182/blood.v75.1.33.bloodjournal75133

Cited by 22 publications

(9 citation statements)

References 1 publication

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“…In order to compare data of this trial with those previously obtained by other authors in the target population [3,5], the 50 % disappearance time and recovery are considered (Table 6). Values of these two parameters defined in the present trial and in other two investigations [3,5] are superimposable.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Behaviour of Antithrombin III Following Intravenous Infusion in Healthy Volunteers

Marzo¹,

Ceppi-Monti²,

Giusti³

et al. 2011

Arzneimittelforschung

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Antithrombin III (CAS 52014-67-2) is produced from plasma of healthy donors and is purified from any detectable agent of transmissible infection. This drug is used in therapy by i.v. route to manage acute thrombotic episodes and to treat patients suffering from its deficiency. The present trial was conducted with the aim to evaluate the pharmacokinetics and the safety of a new preparation of antithrombin III, which in the purification procedure has included a nanofiltration step to increase the safety against the transmission of any agent of infection. The trial was conducted in twelve healthy volunteers of either sex. All the ethics procedures were fully respected, namely the approval from Ethics Committee, the notification to the central regulatory authority, the approval of consent form in writing. Volunteers were hospitalized about 36 h before drug treatment. The baseline situation was investigated throughout the day before the treatment (day-1). On day 1, the drug was infused i.v. for 20 min. Twenty blood samples were drawn from each volunteer, in baseline situation, during and after the infusion. Functional antithrombin III, antithrombin III antigen, prothrombin time, partial thromboplastin time were evaluated in all plasma samples. Both functional antithrombin III and antithrombin III antigen produced well defined plasma concentration-time profiles after the infusion, which allowed net values of these two analytes to be obtained subtracting baseline from post-infusion concentrations. Net pharmacokinetic parameters of functional antithrombin III and antithrombin III antigen proved to be almost superimposable. A comparison of data obtained in this trial on healthy volunteers with those previously obtained by other authors on target population demonstrates similar and fully comparable results. The authors conclude that the nanofiltration step neither affects at all the pharmacokinetics/pharmacodynamics nor the safety of the formulation investigated.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Behaviour of Antithrombin III Following Intravenous Infusion in Healthy Volunteers

Marzo¹,

Ceppi-Monti²,

Giusti³

et al. 2011

Arzneimittelforschung

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“…17,[19][20][21][22][23][24] Patients with both inherited and acquired deficiency have been treated with human plasma-derived AT concentrates. 15,[17][18][19][25][26][27][28][29][30][31][32][33][34][35][36] In AT-deficient patients, supplementation with AT concentrates has been used in situations in which the risk for thromboembolism is very high. For example, hereditary deficient patients have been treated with AT concentrates for prophylaxis of thrombosis postoperatively or during pregnancy and after delivery.…”

Section: Therapeutic Uses Of Atmentioning

confidence: 99%

“…For example, hereditary deficient patients have been treated with AT concentrates for prophylaxis of thrombosis postoperatively or during pregnancy and after delivery. 27 The objective of AT therapy then is to overcome heparin resistance that is presumed to exist in patients who have low levels of circulatory AT. 15 The therapeutic value of AT supplementation with concentrates is more controversial in the case of acquired deficiencies.…”

Section: Therapeutic Uses Of Atmentioning

confidence: 99%

Recombinant Antithrombin: Production and Role in Cardiovascular Disorder

Levy¹,

Weisinger²,

Ziomek³

et al. 2001

Semin Thromb Hemost

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Plasma-derived antithrombin (AT) concentrates have been used for the management of hereditary and acquired deficiencies since the early 1980s. Recombinant versions of other blood factors and their derivatives are increasingly becoming available, providing a safe and abundant supply of these important therapeutics. However, the complexity of the AT molecule and the large doses often required for supplementation treatments preclude the use of traditional cell culture bioreactors for recombinant production. The development of a very efficient expression system has been necessary for the cost-efficient recombinant production of AT. Transgenic production, with its ability to yield high levels of heterologous protein and its scale-up flexibility, is an attractive alternative to plasma fractionation. Purification of recombinant AT from the milk of transgenic dairy goats has been developed to provide a homogeneous, well-defined, and abundant supply of this factor. This article describes the production of recombinant AT and aspects of clinical applications of this molecule to cardiovascular disorders.

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“…The management of patients with both inherited and acquired antithrombin deficiency has advanced considerably with the wide availability of antithrombm concentrates. 191 Because patients with antithrombin deficiency lack the available site of action for heparin, anticoagulation for patients with congenital deficiency who present with acute venous thrombosis or PE with heparin alone is ineffective. Administration of antithrombin concentrates must accompany anticoagulation with heparin.…”

Section: Disorders Both Inherited and Acquired Antithrombinmentioning

confidence: 99%

Treatment of Hereditary and Acquired Thrombophilic Disorders

Baker¹,

Bick²

1999

Semin Thromb Hemost

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The treatment of hereditary and acquired thrombophilic disorders is based on an understanding of the disease pathophysiology, prevalence, associated morbidity and mortality, and available therapeutic options. Genetic mutations are identified that result in activated protein C (APC) resistance and hyperhomocyst(e)inemia. The underlying etiologies are less well-defined; however, the disorders of factor XII deficiency, dysfibrinogenemia, Wien-Penzing platelet defect, and sticky platelet syndrome (SPS) are treatable inherited thrombophilias. Antithrombin deficiency, protein C and protein S deficiencies, and plasminogen deficiency are disorders both inherited and acquired. Antiphospholipid antibodies, myeloproliferative syndromes, and Trousseau's syndrome are acquired. Treatment for acute arterial thrombosis or venous thromboembolism is the same or similar for all thrombophilic disorders. Long-term management is based on the risk of a primary or recurrent acute thrombotic event, compared with the risk of the proposed therapy. Few blinded, controlled studies are available to validate treatment recommendations. When long-term anticoagulation is advised, careful consideration should be given to the risk associated with therapy. Bleeding risk, variable efficacy, and the risk of cutaneous necrosis limit the use of warfarin. Fixed low-dose unfractionated porcine heparin and low-molecular-weight heparins (LMWH) offer significant advantages for long-term management. These recommendations are derived from an analysis of the pertinent medical literature and are expected to change with the progress of clinical and laboratory investigation.

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Evaluation of the safety, recovery, half-life, and clinical efficacy of antithrombin III (human) in patients with hereditary antithrombin III deficiency. Cooperative Study Group [see comments]

Cited by 22 publications

References 1 publication

Pharmacokinetic Behaviour of Antithrombin III Following Intravenous Infusion in Healthy Volunteers

Pharmacokinetic Behaviour of Antithrombin III Following Intravenous Infusion in Healthy Volunteers

Recombinant Antithrombin: Production and Role in Cardiovascular Disorder

Treatment of Hereditary and Acquired Thrombophilic Disorders

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